The overall objective of our research is to understand detailed synaptic mechanisms underlying the center-surround antagonistic receptive field (CSARF) organization of retinal bipolar cells (BCs), and how BCs form parallel information channels for signal processing in the retina. We will use microelectrode voltage recording techniques to study BC receptive field properties in the flat-mounted retina, and use single or dual whole-cell patch clamp techniques to study light-, current/voltage- or neurotransmitter-elicited signals in individual or pairs of morphologically identified cells in retinal slices. These two approaches compensate each other's limitations, and with the new knowledge and technical advances developed during the past grant period, we will use the salamander retina as a model system to study synaptic mechanisms underlying CSARF organization of the four major types of BCs (rod- and cone-dominated depolarizing and hyperpolarizing bipolar cells (DBC-R, DBC-C, HBC-R and HBC-C)) found in most vertebrates. This application addresses 4 specific aims focused on 4 key sets of BC receptive field properties: (1) relative center/surround response strength, receptive field size, degree of coupling and response conductance changes, (2) horizontal cell (HC)-mediated surround inputs in the outer retina (HC-cone feedback and HCBC feedforward synapses, and whether these synapses are chemical or electrical), (3) amacrine cell (AC)-mediated surround inputs in the inner retina (GABAA-, GABAC- and glycine-receptor-mediated AC signals and stratum-by-stratum distributions), and (4) properties of presynaptic voltage-evoked excitatory postsynaptic currents (veEPSCs) in output synapses to ganglion cells. Results obtained will provide a detailed description on how different synaptic pathways mediate the center and surround responses of different types of BCs in the retina, and the differences may render possible explanations for several controversial issues in the BC CSARF synaptic circuitry. As similarities in functional, anatomical and neurochemical organizations between salamander and mammalian retinas become increasingly evident, knowledge obtained from this project will facilitate our understanding on how BC parallel information channels in mammalian and human retinas are organized, and provide important clues for developing animal models for various retinal diseases.